This proposal is concerned with identification of (1) the component(s) of the phospholipid fraction of hepatic microsomes responsible for the inhibition of drug metabolism, (2) the nature and mechanism of this inhibition, (3) the possible interrelationships between the inhibition of drug metabolism and metabolic events in microsomes, and (4) the influence on drug metabolism of unsaturated fatty acids added to nutritionally adequate diets. Preliminary results suggest that a phospholipid component of microsomes containing unsaturated fatty acids is responsible for the inhibition of drug metabolism observed in vitro, and that this inhibitory lipid is present in greater quantities in the liver of the neonatal rat than in that of the adult rat. The goal of this proposal is to delineate the factors, particularly lipoidal in nature, that may be responsible for altered drug metabolism in neonatal and aged rats.